title: Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years.
abstract: OBJECTIVE
  Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women.
  
  
  OBJECTIVE
  To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function.
  
  
  METHODS
  Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999.
  
  
  METHODS
  Forty academic research centers.
  
  
  METHODS
  The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years.
  
  
  METHODS
  The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years.
  
  
  METHODS
  The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory.
  
  
  RESULTS
  Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (−0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of −0.17 (−0.33 to −0.02) and −0.25 (−0.42 to −0.08), respectively; however, this may be a chance finding.
  
  
  CONCLUSIONS
  CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01124773.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.forename: Sally A
authors.initials: SA
authors.lastname: Shumaker
authors.forename: Iris
authors.initials: I
authors.lastname: Leng
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Candice M
authors.initials: CM
authors.lastname: Brown
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.forename: Leslie
authors.initials: L
authors.lastname: Vaughan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Rapp
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D003071:Cognition / Q000187:drug effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000627:therapeutic use; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate